摘要
考察四妙丸中3种生物碱及其4个代谢产物在正常和2型糖尿病模型大鼠体内的排泄动力学差异。通过链脲佐菌素诱导模型大鼠,采用LC-MS/MS检测正常和糖尿病大鼠尿液、粪便和胆汁中生物碱成分,探究糖尿病对四妙丸生物碱排泄过程的影响。结果显示,大鼠口服四妙丸提取物72 h后,粪便为四妙丸中生物碱的主要排泄途径,木兰花碱、小檗碱在正常大鼠的粪便总排泄率分别为4.87%、56.54%,在糖尿病大鼠减小为2.35%、35.53%,差异具有统计学意义(P<0.05);糖尿病大鼠尿液中黄柏碱、木兰花碱和小檗碱的总排泄率明显降低,分别为正常大鼠的53.57%、60.84%、52.78%。口服四妙丸12 h后,糖尿病大鼠胆汁中小檗碱总排泄率明显增加,为正常大鼠的253.33%。糖尿病状态下,小檗碱的代谢产物唐松草酚定在尿液和粪便的总排泄率明显减小,在胆汁中明显增大;药根碱和巴马汀的总尿排率明显增大,t1/2和Ke发生显著改变。结果表明,糖尿病影响四妙丸生物碱的体内过程,使其以原型药物的形式排泄减少,影响小檗碱的生物转化,最终使生物碱体内暴露量增加,这将有利于生物碱发挥降血糖作用。该实验为四妙丸在糖尿病的临床应用和药物开发提供参考。
This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats.The diabetes model was established in rats by injection of streptozotocin,and the alkaloids in urine,feces,and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills.The results showed that 72 h after intragastric administration of the extract of Simiao Pills,feces were the main excretion route of alkaloids from Simiao Pills.The total excretion rates of magnoflorine and berberine in normal rats were 4.87%and 56.54%,which decreased to 2.35%and 35.53%in diabetic rats,which had statistical significance(P<0.05).The total excretion rates of phellodendrine,magnoflorine,and berberine in the urine of diabetic rats decreased significantly,which were 53.57%,60.84%,and 52.78%of those in normal rats,respectively.After 12 h of intragastric administration,the excretion rate of berberine in the bile of diabetic rats increased significantly,which was 253.33%of that of normal rats.In the condition of diabetes,the excretion rate of berberine metabolite,thalifendine significantly decreased in urine and feces,but significantly increased in bile.The total excretion rates of jateorrhizine and palmatine in the urine increased significantly,and t1/2 and Ke changed significantly.The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills,reducing their excretion in the form of prototype drug,affecting the biotransformation of berberine,and ultimately increasing the exposure of alkaloids in vivo,which would be conducive to the hypoglycemic effect of alkaloids.This study provides references for the clinical application and drug development of Simiao Pills in diabetes.
作者
胡艳楠
罗振业
刘昌顺
夏婷
张锋林
陈飞龙
谭晓梅
HU Yan-nan;LUO Zhen-ye;LIU Chang-shun;XIA Ting;ZHANG Feng-lin;CHEN Fei-long;TAN Xiao-mei(Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics,Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology,School of Traditional Chinese Medicine,Southern Medical University,Guangzhou 510515,China)
出处
《中国中药杂志》
CSCD
北大核心
2023年第23期6509-6518,共10页
China Journal of Chinese Materia Medica
基金
国家重点研发计划“中医药现代化研究”专项(2018YFC1704500,2018YFC1704503)。
关键词
四妙丸
生物碱
尿液
粪便
胆汁
排泄
Simiao Pills
alkaloids
urine
feces
bile
excretion
